title: The acid-secreting parietal cell as an endocrine source of Sonic Hedgehog during gastric repair.
abstract: Sonic Hedgehog (Shh) has been shown to regulate wound healing in various tissues. Despite its known function in tissue regeneration, the role of Shh secreted from the gastric epithelium during tissue repair in the stomach remains unknown. Here we tested the hypothesis that Shh secreted from the acid-secreting parietal cell is a fundamental circulating factor that drives gastric repair. A mouse model expressing a parietal cell-specific deletion of Shh (PC-ShhKO) was generated using animals bearing loxP sites flanking exon 2 of the Shh gene (Shh(flx/flx)) and mice expressing a Cre transgene under the control of the H(+),K(+)-ATPase β-subunit promoter. Shh(flx/flx), the H(+),K(+)-ATPase β-subunit promoter, and C57BL/6 mice served as controls. Ulcers were induced via acetic acid injury. At 1, 2, 3, 4, 5, and 7 days after the ulcer induction, gastric tissue and blood samples were collected. Parabiosis experiments were used to establish the effect of circulating Shh on ulcer repair. Control mice exhibited an increased expression of Shh in the gastric tissue and plasma that correlated with the repair of injury within 7 days after surgery. PC-ShhKO mice showed a loss of ulcer repair and reduced Shh tissue and plasma concentrations. In a parabiosis experiment whereby a control mouse was paired with a PC-ShhKO littermate and both animals subjected to gastric injury, a significant increase in the circulating Shh was measured in both parabionts. Elevated circulating Shh concentrations correlated with the repair of gastric ulcers in the PC-ShhKO parabionts. Therefore, the acid-secreting parietal cell within the stomach acts as an endocrine source of Shh during repair.
authors.affiliation: PhD, Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, 231 Albert B. Sabin Way, Room 4255 MSB, Cincinnati, Ohio 45267-0576. yana.zavros@uc.edu.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Engevik
authors.forename: Rui
authors.initials: R
authors.lastname: Feng
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Yana
authors.initials: Y
authors.lastname: Zavros
mesh_terms: D019342:Acetic Acid / Q000633:toxicity; D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010227:Parabiosis; D010295:Parietal Cells, Gastric / Q000378:metabolism*; D013270:Stomach / Q000166:cytology / Q000187:drug effects; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
chemical_list: D053823:Hedgehog Proteins; C465570:Shh protein, mouse; D019342:Acetic Acid